Cryotherapy Methods for Treating Vessel Dissections and Side Branch Occlusion

ABSTRACT

The present invention provides cryotherapy treatment of dissections in a blood vessel of a patient. The present invention further provides cryotherapy treatment of side branch occlusion in a bifurcated blood vessel. One method for treating potential or existing dissections in a blood vessel comprises cooling the blood vessel to a temperature and for a time sufficient to remodel the blood vessel such that dissections of the blood vessel are reduced. Another method for treating side branch occlusion in a bifurcated blood vessel, the bifurcated blood vessel having a side branch and a main branch, the main branch having plaque disposed thereon, comprises cooling an inner surface of the main branch to a temperature and for a time sufficient to inhibit plaque shift from the main branch into the side branch.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 10/867,986filed on Jun. 14, 2004, which is divisional of U.S. patent applicationSer. No. 09/953,500 filed on Sep. 14, 2001, which claims the benefitunder 35 U.S.C. §119(e) of U.S. Provisional Patent Application No.60/312,295 filed on Aug. 13, 2001, the entire contents of each areincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods and kits.More particularly, the present invention provides methods and kits forcryogenically cooling a blood vessel within a patient's vasculature totreat potential or existing dissections in the blood vessel. The presentinvention further provides methods and kits for cryogenically cooling abifurcated blood vessel to treat side branch occlusion. Vesseldissections and side branch occlusion often result from angioplasty orother intravascular procedures for treating atherosclerosis and otherdiseases of the vasculature.

Atherosclerotic plaque is present to some degree in most adults. Plaquescan severely limit the blood flow through a blood vessel by narrowingthe open vessel lumen. This narrowing effect or stenosis is oftenresponsible for ischemic heart disease. Fortunately, a number ofpercutaneous intravascular procedures have been developed for treatingatherosclerotic disease in a patient's vasculature. The most successfulof these treatments is percutaneous transluminal angioplasty (PTA). PTAemploys a catheter having an expansible distal end, usually in the formof an inflatable balloon, to dilate a stenotic region in the vasculatureto restore adequate blood flow beyond the stenosis. Other procedures foropening stenotic regions include directional atherectomy, rotationalatherectomy, laser angioplasty, stents and the like. While thesepercutaneous intravascular procedures, particularly PTA, have providedsignificant benefits for treatment of stenosis caused by plaque, theycontinue to suffer from significant disadvantages. Particularly commondisadvantages are the subsequent occurrence of vessel dissection, vesselrecoil (acute and delayed), side branch occlusion, restenosis, and otherprocedure related trauma. Such disadvantages may affect up to 80% of allangioplasty patients to some extent.

During conventional PTA, the inflated balloon tends to create largefissures or tears in the intima of the blood vessel wall, particularlyat a junction between the plaque and the vessel wall. Such tears orfissures are referred to as dissections. Vessel dissections compromisethe dilated vessel, often constricting or blocking blood flow within thevessel. A number of strategies have been proposed to treat vesseldissections. Previously proposed strategies include prolonged ballooninflation, treatment of the blood vessel with a heated balloon, stentingof the region following balloon angioplasty, and the like. While theseproposal have enjoyed varying levels of success, no one of theseprocedures is proven to be entirely successful. In particular, stentingof the dilated region may address acute problems of intimal dissectionand vessel recoil, however stents are believed to actually cause amarked increase in the degree of intimal restenosis or hyperplasia(re-narrowing of the an artery following an initially successfulangioplasty). This in turn leads to greater late luminal loss,especially in smaller vessels which are more susceptible to re-closuredue to restenosis. Moreover, stents may prove to be an impracticalsolution when dilating long periphery arteries that may require multiplestent placements. Stents may additionally not always be easilymaneuvered to and positioned in dilated regions, especially in thecoronary arteries.

Another limitation associated with angioplasty is side branch occlusionin a bifurcated blood vessel during dilatation of a primary vessellesion. Side branch occlusion can occur by several mechanisms. The “snowplow” effect may be the most common mode of side branch occlusion, inwhich plaque from a primary vessel is literally “plowed” or “shifted”into the adjacent side vessel during dilatation, narrowing or occludingthe side vessel lumen. Known procedures for treating side branchocclusion include the “kissing balloon technique” where two guidingcatheters are positioned in the bifurcated vessel, one in the primaryvessel and the other in the side branch, and the balloons are inflatedsimultaneously or sequentially so that they potentially touch or “kiss.”However, such angioplasty techniques alone or in combination withstents, has not been entirely successful in preventing side branchocclusion.

For these reasons, it would be desirable to provide methods and kits forthe treatment of dissections in a blood vessel. It would be furtherdesirable to provide methods and kits for the treatment of side branchocclusion in a bifurcated blood vessel. The methods should be suitablefor intravascular and intraluminal introduction, preferably via apercutaneous approach. It would be particularly desirable if the newmethods were able to deliver the treatment in a very controlled and safemanner with minimum side effects. At least some of these objectives willbe met by the invention described herein.

2. Description of the Background Art

Cryoplasty methods and devices are described in U.S. patent applicationSer. No. 08/982,824, now U.S. Pat. No. 5,971,979; U.S. patentapplication Ser. No. 09/203,011; U.S. patent application Ser. No.09/510,903, U.S. patent application Ser. No. 09/619,583, assigned to theassignee of the present application. A cryoplasty device and method arealso described in WO 98/38934. Balloon catheters for intravascularcooling or heating a patient are described in U.S. Pat. No. 5,486,208and WO 91/05528. A cryosurgical probe with an inflatable bladder forperforming intrauterine ablation is described in U.S. Pat. No.5,501,681. Cryosurgical probes relying on Joule-Thomson cooling aredescribed in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713;and 3,901,241. Catheters with heated balloons for post-angioplasty andother treatments are described in U.S. Pat. Nos. 5,196,024; 5,191,883;5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752.Cryogenic fluid sources are described in U.S. Pat. Nos. 5,644,502;5,617,739; and 4,336,691. The following U.S. patents may also berelevant to the present invention: U.S. Pat. Nos. 5,458,612; 5,545,195;and 5,733,280.

Side branch occlusion is described by Stephen N. Oesterle in AngioplastyTechniques for Stenoses Involving Coronary Artery Bifurcations, Am JCardiol, vol. 61, pp. 29G-32G (1988); Lefevre et al. in Stenting ofBifurcation Lesions: Classification, Treatments, and Results,Catheterization and Cardiovascular Interventions, vol. 49, pp. 274-283(2000); Chevalier et al. in Placement of Coronary Stent in BifurcationLesions by the “Culotte” Technique, Am J Cardiol, vol. 82, pp. 943G-949G(1998). Cutting balloons are described athttp://www.interventionaltech.com/Products/CuttingBallon.html. The fulldisclosures of each of the above references are incorporated herein byreference.

BRIEF SUMMARY OF THE INVENTION

The present invention provides cryotherapy treatment of dissections in ablood vessel of a patient. The present invention further providescryotherapy treatment of side branch occlusion in a bifurcated bloodvessel. The blood vessel may be any blood vessel in the patient'svasculature, including veins, arteries, and particularly coronaryarteries. The blood vessel will be at least partially stenosed,typically by eccentric calcified plaque (i.e. the plaque compromises avessel lumen predominantly from one side) in the coronary and peripheralarteries. In particular, the present invention may limit, reduce,minimize, prevent, mitigate, and/or inhibit potential or existingdissections of a vessel and/or plaque shift from a main branch into aside branch of a bifurcated blood vessel so as to inhibit acute coronarysyndrome.

In a first aspect, the present invention provides a method for treatingpotential or existing dissections in a blood vessel. The methodcomprises cooling the blood vessel to a temperature and for a timesufficient to remodel the blood vessel such that dissections of theblood vessel are reduced. The cooling treatment will often be directedagainst all or a portion of a circumferential surface of a lumen of theblood vessel.

Cooling of a vessel may be effected by introducing a catheter into alumen of a blood vessel. A balloon is positioned within the vessel lumenadjacent the potential or existing dissection. Cryogenic cooling fluidis introduced into the balloon and exhausted. The balloon expands toradially engage the vessel lumen. Generally, the cooling temperature atthe cell surface of the blood vessel lumen is in a range from about −3°C. to about −15° C. The tissue is typically maintained at the desiredtemperature for a time period in the range from about 10 seconds toabout 60 seconds, more preferably from about 20 seconds to 40 seconds.Vessel dissection treatment may be enhanced by repeating cooling incycles, typically with from about 1 cycle to 3 cycles, with the cyclesbeing repeated at a rate of about one cycle every 60 seconds.

The dissections may comprise flaps, residual plaque, and/or pieces oftissue resulting from fissuring or tearing of the intima of the bloodvessel wall or plaque thereon. Typically, such dissections occur at ajunction between the plaque and the vessel wall, wherein the plaquetears at its margins and sends a plane of dissection deep into the mediaof the vessel wall. Dissections are undesirable as they often compromisethe integrity of the blood vessel by at least partially blocking theblood vessel. Such blockage can limit blood flow and potentially createa threat to acute vessel closure. The dissections may further createflow in an abnormal pattern (i.e. flow in planes other than the truevessel lumen or non laminar flow.)

The blood vessel is subject to dissections resulting from treatment of astenosis, wherein the treatment of the stenosis typically comprisespercutaneous transluminal angioplasty. The cooling step may be performedbefore or after balloon angioplasty, and will preferably be performedduring balloon angioplasty. Surprisingly, work in connection with thepresent invention has shown that cooling of the blood vessel reducesand/or inhibits potential or existing dissections so as to produce a“stent-like” angiographic result (i.e. dissection free lumen without theuse of a stent). Moreover, cooling may further minimize or inhibitrestenosis or hyperplasia (re-narrowing of the an artery following aninitially successful angioplasty) and help maintain the patency of abody lumen. Cooling may also be efficiently effected in long peripheryarteries and the cooling apparatus easily maneuvered to and positionedin the treatment vessel, especially in the coronary arteries, so thatcooling may be effected in difficult to access areas.

The cooling step may alter mechanical properties of the blood vesselwall or plaque thereon so the that fissuring or tearing of the bloodvessel wall or plaque thereon is reduced. Particularly, the blood vesselwall and/or plaque is solidified so that there is not such a greatdisparity in compliance between the two. As such, the dilatation forceapplied by the angioplasty cooling balloon is more evenly distributedaround a circumference of the vessel wall so that tearing of the vesselat the junction between the vessel wall and plaque is minimized (i.e.any resulting fissures in the vessel wall and plaque are small or microcracks that do not compromise flow in the vessel). Cooling may alsoalter a fail mode of the vessel resulting from the modified mechanicalproperties. Cooling may alternatively or additionally enhance bondingbetween layers of the blood vessel wall so that fissuring or tearing ofthe blood vessel wall is reduced. In other applications, the coolingstep may tack or re-attach existing vessel dissections, resulting from aprior angioplasty procedure, into the blood vessel wall.

In some instances, cooling may soften or weaken the vessel wall orplaque thereon, particularly eccentric calcified plaque, so that thevessel can be dilated or expanded at much lower pressures than is usedwith conventional angioplasty. Specifically, cooling temperatures ofabout −10° C. may freeze fluid between spaces in the calcium which inturn breaks up the calcified plaque, softening the vessel so that it candilated at a lower pressure. In addition to the softening or weakeningof the vessel wall or plaque thereon, cooling at low temperatures mayalso freeze and harden non-treatment tissue adjacent to the calcifiedplaque so that the vessel wall may exhibit more uniform propertiesagainst the dilation force applied by the angioplasty cooling balloon.

In another aspect, the present invention provides a method for treatingpotential or existing dissections in a blood vessel, said methodcomprising introducing a catheter into a lumen of the blood vessel andpositioning a balloon within the vessel lumen adjacent the potential orexisting dissection. Cryogenic cooling fluid is introduced into theballoon and exhausted. The balloon is expanded to radially engage thevessel lumen and cool the vessel lumen to a temperature and for a timesufficient to remodel the blood vessel such that dissections of theblood vessel are reduced and/or inhibited. Cooling may comprise adheringthe cooling balloon to the blood vessel or plaque thereon so as tominimize any slippage of the cooling balloon. This is particularlyadvantageous in the treatment of a stenosis as plaque is often amorphousand slippery and as such conventional uncooled angioplasty balloonsoften slip and cause additional dissections or tears proximal and distalof the stenosis. Hence, cooling prevents the creation of any additionaldissections by minimizing such slippage of the cooling balloon and in sodoing further allows for controlled dilatation at the stenosis.

In another aspect, the present invention provides a method for treatingside branch occlusion in a bifurcated blood vessel, the bifurcated bloodvessel having a side branch and a main branch, the main branch havingplaque disposed thereon. In some instances, the side branch may also beat least partially stenosed. The method comprises introducing a catheterinto a lumen of the main branch and positioning a balloon within themain branch adjacent the plaque. Cryogenic cooling fluid is introducedinto the balloon and exhausted. The balloon is expanded to radiallyengage the main branch lumen and an inner surface of the main branch iscooled to a temperature and for a time sufficient to inhibit plaqueshift from the main or primary branch into the adjacent or side branch.

The plaque comprises a combination of calcified, fatty, and fibroustissues and is fairly amorphous and slippery so that it easily shifts byits structural nature. As such, the side branch is often subject toocclusion by plaque shift from the main branch into the side branch as aresult of treatment of plaque in the main branch. Treatment of theplaque typically comprises balloon angioplasty, wherein the cooling stepmay be performed before, after, or preferably during balloonangioplasty. In some instances, the treatment of plaque in the mainbranch may be accompanied by simultaneous or sequential treatment ofstenosis in the side branch. It is believed that the cooling step altersmechanical properties of the plaque (i.e. plaque compliance) so thatplaque shift from the main branch to the side branch is inhibited. Inparticular, cooling may solidify the plaque so that it less amorphousand thus less susceptible to shifting. Plaque solidification may furtherbe enhanced by the formation of a temporary ice cap on an orifice of theside branch due to a small portion of the cryoplasty balloon coming intocontact with blood cells.

In yet another aspect, the present invention provides a kit for treatingpotential or existing dissections in a blood vessel. The kit comprises acatheter having a proximal end, a distal end, and a cooling member.Instructions are included in the kit for use of the catheter. Theseinstructions may comprise the step of cooling the blood vessel adjacentthe potential or existing dissection to remodel the blood vessel suchthat dissections of the blood vessel are reduced. The kit mayadditionally or alternatively provide for the treatment of side branchocclusion in a bifurcate vessel, wherein the instructions recite thestep of cooling a main branch lumen adjacent the plaque to inhibitplaque shift from the main branch into the side branch. Such kits mayinclude instructions for performing one or more of the above describedmethods. The instructions will often be printed, optionally being atleast in-part disposed on packaging. The instructions may alternativelycomprise a videotape, a CD-ROM or other machine readable code, agraphical representation, or the like showing any of the above describedmethods.

In another aspect, the present invention provides a method for treatingpotential elastic recoil in a blood vessel, the method comprisingintroducing a catheter into a lumen of the blood vessel and positioninga balloon within the vessel lumen adjacent tissue that may potentiallyrecoil. The balloon is expanded to radially engage the vessel lumen andcool the vessel lumen to a temperature and for a time sufficient toremodel the blood vessel such that actual elastic recoil is inhibited.

The cooling step may alter structural properties of collagen fibers ofthe vessel wall such that elastic recoil of the vessel is reduced. Inparticular, induction of a phase change in an aqueous component of theadjacent tissue during cooling may cause acute structural changes to thetissue matrix. Dilatation of the vessel by the cooling balloon may beaccompanied by a drop in a balloon surface temperature below a phasetransition threshold of physiologic saline. Thus, as the balloon expandsand experiences a temperature drop, the aqueous saline in interstitialspaces (i.e. spaces between cells and fibers that constitute the vesselwall) in the adjacent tissue begin to freeze. As such, ice may benucleated in the interstitial spaces and propagate radially outwardthrough the tissue. The expanding ice may in turn impose mechanicalcompressive forces on collagen fibers and vessel cells. Correspondingly,the collagen fibers and cells may undergo morphological deformation inresponse to the mechanical forces. Any plastic deformation of thecollagen fibers may produce permanent or semi-permanent alteration ofthe vessel tissue, and consequently may yield an alternation in thestructural properties of the tissue. Specifically, possible compactingor compression of collagen fibers by cooling may substantially alterstructural properties, such as elasticity, of the collagen fibers sothat elastic recoil of the vessel is reduced.

The blood vessel is typically subject to elastic recoil resulting fromtreatment of a stenosis. The treatment of stenosis typically comprisesballoon angioplasty, wherein the cooling step may be performed before,after, or preferably during balloon angioplasty. Moreover, duringballoon angioplasty the vessel is being expanded by balloon expansionwhich may exert radially directed mechanical forces on the vesseltissue. Hence, the dual action of mechanical compressive forcesgenerated by concurrent dilation and cooling may produce a morebeneficial effect than can be achieved by conventional angioplasty.

In a still further aspect, the present invention provides a method forproducing a smooth luminal surface in a blood vessel that is at leastpartially stenosed by fatty plaque, said method comprising introducing acatheter in a lumen of the blood vessel and positioning a balloon withinthe vessel lumen adjacent the fatty plaque. The balloon is expanded toradially engage the vessel lumen and cool the vessel lumen to atemperature and for a time sufficient to remodel the blood vessel so asto produce a smooth luminal surface. In particular, fatty lipid basedplaque may undergo chemical or physical alterations in response tocooling of the plaque below a lipid phase change temperature (typicallybeing in a range from about +15° C. to about 0° C.). This remodeling ofthe vessel and plaque thereon may in turn produce a smoother luminalsurface than can be achieved with conventional angioplasty. A smootherluminal surface advantageously provides more laminar flow through thevessel wall, and further reduces any shear stresses on the vessel wall.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C are cross-sectional views of blood vessels havingdissections.

FIG. 2A is a cross-sectional view of a stenosed bifurcated blood vessel.

FIG. 2B is a cross-sectional view illustrating plaque shift in thebifurcated blood vessel.

FIG. 3 illustrates a cryotherapy catheter for treating vesseldissections and side branch occlusion constructed in accordance with theprinciples of the present invention.

FIG. 4 is a cross-sectional view of the catheter taken along line 4-4 inFIG. 3.

FIG. 5 is a functional flow diagram illustrating the operation ofautomatic fluid shutoff mechanism of the catheter of FIG. 3.

FIGS. 6 and 7 illustrate a handle and removable energy pack for use inthe cryotherapy catheter of FIG. 3.

FIGS. 8A-8D illustrate use of the catheter of FIG. 3 for treatment ofpotential vessel dissections.

FIGS. 9A-9C illustrate use of the catheter of FIG. 3 for treatment ofexisting vessel dissections.

FIGS. 10-10C illustrate use of the catheter of FIG. 3 for treatment ofside branch occlusion.

FIG. 11 illustrates a vessel dissection or side branch occlusiontreatment kit including the apparatus of FIG. 3 and instructions foruse.

FIGS. 12A through 13E are angiographic results of experiments showing anactual and observed reduction in stenosis with a minimum amount ofvessel dissection and side branch occlusion as described in the twoExperimental sections provided hereinbelow.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides cryotherapy treatment of dissections in ablood vessel of a patient. FIGS. 1A-1C illustrate cross-sectional viewsof a blood vessel 100 having dissections 102 within a lumen 104 of thevessel. The dissections 102 generally comprise flaps, residual plaque,and/or pieces of tissue resulting from fissuring or tearing of theintima of the blood vessel wall or plaque thereon from primarytreatments like balloon angioplasty. Typically, such dissections 102occur at a junction between the plaque and the vessel wall, wherein theplaque tears at its margins and sends a plane of dissection deep intothe media of the vessel wall. As shown in FIG. 1B, dissections 102 areundesirable as they often compromise the integrity of the blood vesselby at least partially blocking the blood vessel 100. For example, thedissection 102 may shift in direction 106 to limit blood flow andpotentially create a threat to acute vessel closure (FIG. 1B).Dissections 102 may further create flow in planes other than the truevessel lumen as depicted by arrow 108.

The present invention further provides cryotherapy treatment of sidebranch occlusion in a bifurcated vessel. FIG. 2A illustrates abifurcated blood vessel having a main or primary branch 112 and anadjacent or side branch 114. The main branch 112 is at least partiallystenosed 116. The plaque 116 generally comprises a combination ofcalcium, fat, and lipids and is fairly amorphous and slippery so that iteasily shifts by its structural nature. As such, the side branch 114 isoften subject to occlusion by plaque shift from the main branch 112 intothe side branch 114, as depicted by arrows 118, as a result of treatmentof plaque in the main branch. Treatment of plaque typically comprisesballoon angioplasty, wherein balloon dilatation shifts the plaque 116into the side branch 114 as shown in FIG. 2B, narrowing or occluding theside branch lumen and potentially creating a threat to acute vesselclosure.

Referring now to FIGS. 3 and 4, a cryotherapy catheter 10 (which is morefully described in co-pending application Ser. No. 09/619,583 filed Jul.19, 2000, the full disclosure of which is incorporated herein byreference) for treating dissections 102 in a blood vessel 100 (see FIG.1A) and/or side branch occlusion (see FIG. 2B) will be described. Thecatheter 10 comprises a catheter body 12 having a proximal end 14 and adistal end 16 with a cooling fluid supply lumen 18 and an exhaust lumen20 extending therebetween. A first balloon 22 is disposed near thedistal end of the catheter body 12 in fluid communication with thesupply and exhaust lumens. A second balloon 24 is disposed over thefirst balloon 22 with a thermal barrier 26 therebetween. It will beappreciated that the following depictions are for illustration purposesonly and does not necessarily reflect the actual shape, size, ordimensions of the cryotherapy catheter 10. This applies to alldepictions hereinafter.

The balloons 22, 24 may be an integral extension of the catheter body12, but such a structure is not required by the present invention. Theballoons 22, 24 could be formed from the same or a different material asthe catheter body 12 and, in the latter case, attached to the distal end16 of the catheter body 12 by suitable adhesives, heat welding, or thelike. The catheter body 12 may be formed from conventional materials,such as polyethylenes, polyimides, and copolymers and derivativesthereof. The balloons 22, 24 may also be formed from conventionalmaterials used for angioplasty, preferably being inelastic, such asnylon, polyethylene terephthalate (PET), or polyethylene, elastic, suchas urethane, latex, or silicone, or other medical grade materialsuitable for constructing a strong non-distensible balloon.Additionally, balloons 22 and 24 could be formed from different materialto provide improved protection. For example, the first balloon 22 couldbe formed from PET to provide strength while the second balloon 24 couldbe formed from polyethylene to provide durability. The balloons 22, 24have a length of at least 1 cm each, more preferably in the range from 2cm to 5 cm each in a coronary artery and 2 cm to 10 cm each in aperiphery artery. The balloons 22, 24 will have diameters in the rangefrom 2 mm to 5 mm each in a coronary artery and 2 mm to 10 mm each in aperipheral artery.

The thermal barrier 26 may comprise a gap maintained between theballoons 22, 24 by a filament. The filament typically comprises ahelically wound, braided, woven, or knotted monofilament. Themonofilament may be formed from PET or polyethylene napthlate (PEN), andaffixed to the first balloon 22 by adhesion bonding, heat welding,fasteners, or the like. The thermal barrier 26 may also comprise a gapmaintained between the balloons 22, 24 by a plurality of bumps on anouter surface of the first balloon 22 and/or an inner surface of thesecond balloon 24. The plurality of bumps may be formed in a variety ofways. For example, the bumps may be intrinsic to the balloon (createdduring balloon blowing), or the bumps could be created by deforming thematerial of the balloon wall, by affixing mechanical “dots” to theballoon using adhesion bonding, heat welding, fasteners, or the like.Alternatively, the thermal barrier 26 may comprise a gap maintainedbetween the balloons 22, 24 by a sleeve. The sleeve may be perforatedand formed from PET or rubbers such as silicone and polyurethane.

Hubs 34 and 36 are secured to the proximal end 14 of the catheter body12. Hub 34 provides a port 38 for connecting a cryogenic fluid source tothe fluid supply lumen 18 which in turn is in fluid communication withthe inner surface of the first balloon 22. Hub 34 further provides aport 40 for exhausting the cryogenic fluid which travels from balloon 22in a proximal direction through the exhaust lumen 20. Hub 36 provides aport 42 for a guidewire which extends through a guidewire lumen 44 inthe catheter body 12. Typically, the guidewire lumen 44 will extendthrough the exhaust lumen 20, as shown in FIG. 4. The guidewire lumen 44may also extend axially outside the exhaust lumen 20 to minimize theoccurrence of cryogenic fluid entering the blood stream via theguidewire lumen 44. Optionally, the guidewire lumen 44 may extendoutside the inner surface of the first balloon 22 or the guidewire lumen44 may allow for a guidewire to extend outside both balloons 22, 24.Additionally, a reinforcing coil 46 may extend along the catheter body12 proximal the first balloon 22. The reinforcing coil 46 may comprise asimple spring having a length typically in the range from 6 cm to 10 cmto prevent the catheter 10 from kinking up inside the blood vessel.

The cryotherapy catheter 10 in FIG. 3 additionally illustrates a safetymechanism that monitors the containment of the first and second balloons22, 24. The first balloon 22 defines a volume in fluid communicationwith the supply and exhaust lumens. A fluid shutoff is coupled to acryogenic fluid supply with the supply lumen 18. The second balloon 24is disposed over the first balloon 22 with a vacuum space 52therebetween. The vacuum space 52 is coupled to the fluid shutoff so asto inhibit flow of cryogenic fluid into the first balloon 22 in responseto a change in the vacuum space 52.

FIG. 5 illustrates a functional flow diagram of the automatic fluidshutoff mechanism 54. The fluid shutoff 54 typically comprises a vacuumswitch 56 connected to a shutoff valve 58 by a circuit, the circuitbeing powered by a battery 60. The switch 56 may remain closed only whena predetermined level of vacuum space 52 is detected in the secondballoon 24. The closed switch 56 allows the shutoff valve 58, in fluidcommunication with the cryogenic fluid supply 62, to be open.Alternatively, the circuit may be arranged so that the switch 56 is openonly when the predetermined vacuum space 52 is present, with the shutoffvalve 58 being open when the switch is open. The vacuum space 52 isreduced when either the first balloon 22 is punctured, allowingcryogenic fluid to enter the vacuum space 52, or the second balloon 24is punctured, allowing blood to enter the vacuum space 52. In additionto monitoring the containment of both balloons 22, 24, in the event of afailure, the vacuum switch 56 will be triggered to prevent the deliveryof additional cryogenic fluid from the fluid supply 62 into the supplylumen 18. The second balloon 24 also acts to contain any cryogenic fluidthat may have escaped the first balloon 22. The exhaust lumen 20 isfluidly connected to a pressure relief valve 21 which in turn willtypically vent to atmosphere. In some instances, a pressure transducer23 will also trigger the shutoff valve 58 when a particular thresholdpressure is measured.

The vacuum space 52 may be provided by a simple fixed vacuum chamber 64coupled to the vacuum space 52 by a vacuum lumen 66 of the body 12 via avacuum port 68 (See FIG. 3). In one embodiment, a positive displacementpump (ideally being similar to a syringe) is disposed within handle 74and may be actuated by actuator 75, as seen in FIG. 6. The vacuum space52 should comprise a small volume of vacuum in the range from 1 mL to100 mL, preferably 10 mL or less, as a smaller vacuum space 52facilitates detection of a change in the amount of vacuum when a smallamount of fluid leakage occurs. The battery may be electrically coupledto a heater 61 for heating the fluid supply 62 and cryogenic fluidtherein to room temperature or warmer so as to enhance the fluidpressure and cooling system performance, as is more fully described inco-pending application Ser. No. 09/268,205, the full disclosure of whichis incorporated herein by reference. The cryogenic fluid supply 62,heater 61, and battery 60 for powering the circuit may be packagedtogether in an energy pack 70, as seen in FIG. 7. The energy pack 70 isdetachable from a proximal handle 74 of the catheter body anddisposable. A plurality of separate replaceable energy packs 70 allowfor multiple cryogenic cooling cycles. Additionally, an audio alert orbuzzer 76 may be located on the handle 74, with the buzzer providing anaudio warning unless the handle is maintained sufficiently upright toallow flow from the fluid supply 62. The cryotherapy catheter mayadditionally comprise a hypsometer 72 coupled to the volume by athermistor (via thermistor wires 71), thermocouple, or the like locatedin the first balloon 22 or handle to determine the pressure and/ortemperature of fluid in the first balloon 22. The hypsometer allows foraccurate real time measurements of variables (pressure, temperature)that effect the efficacy and safety of cryotherapy treatments.

Referring now to FIGS. 8A through 8D, use of the cryotherapy catheter 10of FIG. 3 for treatment of potential vessel dissections 102 will bedescribed. As illustrated in FIGS. 8A and 8B, catheter 10 will beintroduced into a lumen 104 of the blood vessel 100 over a guidewire GW.The blood vessel 100 may be any blood vessel in the patient'svasculature, including veins, arteries, and particularly coronaryarteries. The blood vessel 100 will typically be at least partiallystenosed 116. The first balloon 22 is positioned within the blood vessellumen 104 adjacent the potential dissection 102. Cryogenic cooling fluidis introduced into the first balloon 22 (in which it often vaporizes)and exhausted. The second balloon 24 expands to radially engage thevessel wall, as illustrated by FIG. 8C. The vaporized fluid serves toinflate balloon 22 (and expand balloon 24) so as to simultaneouslydilate and cool the stenosed blood vessel 100. The blood vessel 100 iscooled to a temperature and for a time sufficient to remodel the bloodvessel such that dissections 102 of the blood vessel wall 100 arereduced. The cooling treatment will be directed at all or a portion of acircumferential surface the vessel lumen 104.

Preferably cooling will reduce and/or inhibit potential dissections soas to produce a “stent-like” angiographic result (i.e. dissection freelumen without the use of a stent), as shown in FIG. 8D. Cooling mayalter mechanical properties of the blood vessel 100′ or plaque 116′thereon so the that fissuring or tearing of the blood vessel wall orplaque thereon is reduced. Particularly, the blood vessel wall 100′and/or plaque 116′ is solidified so that there is not such a greatdisparity in compliance between the two. As such, the dilatation forceapplied by the angioplasty cooling balloon is more evenly distributed sothat tearing of the vessel at the junction between the vessel wall andplaque is minimized. Cooling may further enhance bonding between layerof the blood vessel wall 100′ (i.e., intimal layer, medial layer,adventitial layer) so that fissuring or tearing of the blood vessel wallis reduced. Heat transfer will also be inhibited between the first andsecond balloons 22, 24 by the thermal barrier 26 so as to limit coolingto a desired temperature profile. Additionally, containment of the firstand second balloons 22, 24 will be monitored during cooling by the fluidshutoff mechanism (see FIG. 5).

Suitable cryogenic fluids will preferably be non-toxic and may includeliquid nitrous oxide, liquid carbon dioxide, cooled saline and the like.The cryogenic fluid will flow through the supply lumen 18 as a liquid atan elevated pressure and will vaporize at a lower pressure within thefirst balloon 22. For nitrous oxide, a delivery pressure within thesupply lumen 18 will typically be in the range from 600 psi to 1000 psiat a temperature below the associated boiling point. After vaporization,the nitrous oxide gas within the first balloon 22 near its center willhave a pressure typically in the range from 50 psi to 150 psi.Preferably, the nitrous oxide gas will have a pressure in the range from75 psi to 125 psi in a peripheral artery and a range from about 75 psito 125 psi in a coronary artery.

Generally, the temperature of the outer surface of the first balloon 22will be in a range from about 0° C. to about −50° C. Preferably, thetemperature of the outer surface of the first balloon 22 in a peripheralartery will be in a range from about 0° C. to about −40° C. Thetemperature of the outer surface of the second balloon 24 will be in arange from about −3° C. to about −15° C. This will provide a desiredtreatment temperature in a range from about −3° C. to about −15° C. Thetissue is typically maintained at the desired temperature for a timeperiod in the range from about 1 to 60 seconds, preferably being from 20to 40 seconds. Vessel dissection minimization may be further enhanced byrepeating cooling in cycles, typically with from about 1 to 3 cycles,with the cycles being repeated at a rate of about one cycle every 60seconds.

Referring now to FIGS. 9A through 9C, the cooling step may also tack orre-attach existing vessel dissections 102 resulting from a priorangioplasty procedure into the blood vessel wall 100 to produce a“stent-like” angiographic result, as shown in FIG. 9C. Cooling mayadditionally comprise adhering the cooling balloon 24 to the bloodvessel or plaque thereon so as to minimize any slippage of the coolingballoon and in so doing further allow for controlled dilatation of thevessel.

Referring now to FIGS. 10A through 10C, use of the cryotherapy catheter10 of FIG. 3 for treatment of side branch occlusion in a bifurcatedblood vessel 110 will be described. As illustrated in FIG. 10A, thebifurcated blood vessel 110 has a side branch 114 and a main branch 112,the main branch 112 having plaque 116 disposed thereon. In someinstances, the side branch 114 may also be at least partially stenosed116. A catheter 10 is introduced into a lumen of the main branch 112 anda first balloon 22 positioned within the main branch 112 adjacent theplaque 116. Cryogenic cooling fluid is introduced into the balloon 22and exhausted. A second balloon 24 is expanded to radially engage themain branch lumen, as seen in FIG. 10B, and an inner surface of the mainbranch 112 is dilated and cooled to a temperature and for a timesufficient to inhibit plaque shift from the main or primary branch 112into the adjacent or side branch 114. Cooling may alter mechanicalproperties of the plaque 116′ (i.e. plaque compliance) so that plaqueshift from the main branch 112 to the side branch 114 is inhibited, asseen in FIG. 10C. In particular, cooling may solidify the plaque 116′ sothat it is less amorphous and thus less susceptible to shifting. Plaquesolidification 116′ may further be enhanced by the formation of atemporary ice cap on an orifice of the side branch 114 due to a smallportion of the cryoplasty balloon 24 coming into contact with bloodcells (not shown).

A kit 126 including a catheter 10 and instructions for use 128 isillustrated in FIG. 11. Catheter 10 may comprise the dual ballooncatheter of FIG. 3 or a catheter having a proximal end, a distal end,and a cooling member near its distal end.

Instructions for use 128 may describe any of the associated method stepsset forth above for treatment of vessel dissections and/or side branchocclusion. Instructions for use 128 will often be printed, optionallyappearing at least in part on a sterile package 130 for balloon catheter10. In alternative embodiments, instructions for use 128 may comprise amachine readable code, digital or analog data graphically illustratingor demonstrating the use of balloon catheter 10 to treat vesseldissections and/or side branch occlusion. Still further alternatives arepossible, including printing of the instructions for use on packaging132 of kit 126, and the like. In the following Experimental sections,protocol and results of human clinical studies are given. In particular,angiographic images show a baseline where a significant amount of plaqueis present within a lumen of a vessel wall, particularly the superficialfemoral artery or popliteal artery. The effects of cryoplasty dilatationare captured by another set of angiographic images which generally showalleviation of the stenotic condition with a minimum amount of vesseldissection and side branch occlusion.

Experimental I: Peripheral Cryoplasty Clinical Experience Purpose

Human clinical cases were conducted to evaluate the safety andeffectiveness of the CVSi CryoPlasty Catheter and Cryolnflation Unit inthe dilation of stenotic lesions in diseased superficial femoral andpopliteal arteries. Patients with peripheral vascular disease weretreated with the CVSi CryoPasty System. This was a non-randomizedregistry of fourteen (14) patients.

Patient Selection

The interventionalists for these cases identified patients with stenoticlesions in the superficial femoral artery (SFA) and popliteal arteries,which were amenable to percutaneous treatment. Eligibility requirementsincluded the following: the patient was at least 18 years of age; thepatient had stenotic lesions within the SFA or popliteal artery whichrequired treatment; the target lesion contained a stenosis between 50%and 100%; the patient had a clinical examination within one month priorto treatment including ABI measurement. Patients were excluded if any ofthe following applied: the patient had an evolving myocardialinfarction, or suffered a myocardial infarction within the past 48hours; the patient was participating currently in anotherinvestigational drug or device trial; or the patient suffered a strokeor transient ischemic neurological attack (TIA) within the past twomonths.

Equipment

Equipment used for these cases may be found in any interventionalcatheterization laboratory (including but not limited to fluoroscopyunit with cine film acquisition; sterile accessories such as sheaths andguidewires). The test equipment was the CVSi CryoPlasty System, which iscomposed of the CryoPlasty Catheter, Cryolnflation Unit and accessories(battery, battery receptacle, nitrous oxide cylinder). The operatingparameters of the current cases are treatment time of 50 seconds andsurface temperature of −10±5° C.

Methods

Procedures used were no different than typical interventionalpercutaneous transluminal angioplasty (PTA) procedures. Theinvestigators had a thorough understanding of the technical principals,clinical applications, and risks associated with PTA. In addition,training on the CVSi CryoPlasty System and its Instructions For Use weregiven prior to clinical use of the device. After diagnostic angiographyof the target vessel confirmed the presence of a lesion suitable forendovascular therapy, the patients received the following treatment. Thepatient was pre-treated with conventional doses of heparin and aspirin.Baseline angiographic images were recorded as illustrated in FIGS. 12Athrough 12L. The operators chose whether or not to predilate the lesionwith other percutaneous transluminal devices. If they did predilate, anangiographic image of the interim outcome was recorded. Next, the CVSiCryoPlasty Catheter was advanced across the lesion, and inflated withthe Cryolnflation Unit. After deflation, the catheter was eitherrepositioned for additional cryoinflations, or removed. At theconclusion of the procedure, final cryoplasty angiograms were recordedas illustrated in FIGS. 12A through 12L.

Data Collection

Results of the percutaneous interventions were assessed for acuteoutcomes and in-hospital adverse events. Baseline and post-cryoplastydilation angiography were compared in each treated section. In addition,ankle-brachial indexes (ABI) were measured and recorded prior tointervention, 24 hours post-intervention, and at one-month (see ResultsTable I). ABI is an assessment of flow distal to the treated sections.Technical success was based primarily on the acute angiographicappearance and flow characteristics (24-hour ABI) immediatelypost-cryoplasty dilation compared to the baseline image and thepre-procedural ABI, respectively.

RESULTS TABLE I CLINICAL SUMMARY OF PERIPHERAL PATIENTS Ankle-BrachialPatient Age/ Lesion Indices No. Gender Site Description Pre 24 hr 1M 1G65 yr LSFA 80% stenosis distal to stent, 0.70 1 1 M (ISR) 90% stenosisproximal to stent 2G 88 yr LSFA- Total occlusion, 10-12 cm 0.30 0.30 0 Fpop 3G 74 yr LSFA 98% stenosis with calcified plaque 0.65 1 1 M 4G 75 yrLSFA (4) subtotal focal occlusions, 0.70 1 1 M calcified, 8-10 cm totallength 5G 61 yr R pop 70% focal stenosis 0.70 1 1 M 6G 67 yr L popSubtotal popliteal occlusion, 0.25 0.70 1 F 12-15 cm long 1C 52 yr RSFA70% stenotis, focal calcified lesion 0.75 1 1 M 2C 61 yr L pop 15 mmlong, 80% stenotic lesion in 0.70 1.06 1 F proximal popliteal and a 10mm long, 50% stenotic lesion in the mid popliteal 3C 63 yr LSFA 10 mmlong, 70% stenotic lesion in 0.85 1.06 1 M the proximal SFA and a 10 mmlong, 80% stenotic lesion in the distal SFA 4C 41 yr Right heavilycalcified sub-occlusive 0.60 1.0 1 M com. focal lesion inthe rightcommon fem. femoral artery (15 mm long, 90% stenotic) 5C 73 yr LSFA-diffuse sub-occlusive (12-16 cm 0.57 0.84 0.75 F pop long, 70-80%stenotic) disease in proximal to distal SFA, and 2 focal occlusivelesions in mid popliteal artery 6C 74 yr LSFA 6-8 cm long totalocclusion 0.57 0.85 0.80 F 7C 57 yr LSFA- calcified focal lesions in SFA0.58 0.89 0.97 M pop (15 mm long, 80% stenotic) and in proximalpopliteal artery (10 mm long, 70% stenotic). 8C 61 yr RSFA two adjacent95% stenotic focal 0.60 1.08 0.90 M lesions

Conclusions and Discussion

Procedural safety was demonstrated by the absence of any incidence ofacute serious adverse events or acute percutaneous access site andhemorrhagic adverse events. Investigators were able to use theCryoPlasty device for primary treatment (i.e. were able to cross severestenosis and dilate the lesion with the CVSi device without predilation)in ten of the fourteen cases (71%). Twelve of the fourteen cases (86%)were technical successes based on acute angiographic appearance and flowcharacteristics, with <30% residual stenosis by visual assessment of thefinal angiographic results in the treated segments. Within that 12patient subset of technical success, the 24-hour post-procedural ABIshowed improved blood flow to the lower extremity compared to thepre-procedural measurement. Bail-out stenting was not required in any ofthe cryotreated segments. Some observations that were noted thatcontributed to the high technical success rate were minimum amount ofvessel dissection post-CryoPlasty dilation (also known as “vesselannealing”) and maintained patency of the side branch and collateralvessels at the treated segments (no/minimal plaque shift), asillustrated in FIGS. 12A through 12L and the ABI data in Results TableI.

The registry demonstrated the safety and effectiveness of the CVSiCryoPlasty System in the dilation of stenotic lesions in diseasedvessels, and brought to light some distinct advantages of CryoPlastyover conventional PTA dilation that often requires bail-out stenting dueto dissection or poor flow characteristics.

Experimental II: Coronary Cryoplasty Clinical Experience Purpose

Five patients with coronary artery disease were treated with the CVSiCryoPlasty System to evaluate the safety and effectiveness of the CVSiSystem in the treatment of de novo and in-stent restenotic lesions.Patients were assessed for acute outcomes and in-hospital adverseevents.

Patient Selection

Patients with either a de novo or in-stent restenosis lesion in acoronary artery that was amenable to percutaneous treatment wereidentified by experienced intervention-alists. Lesion inclusion criteriawas very broad and included very complex lesions, such as, lesionlengths ranging from 10 mm to 25 mm, stenoses from 90% to totalocclusions, and calcified, fibrotic, and soft plaque. Other contributingfactors were severe access angulations, high cholesterol, diabetes, andsmoking.

Methods

After diagnostic angiography of the target vessel confirmed the presenceof a lesion suitable for endovascular therapy, each patient received thefollowing treatment. The patient was pretreated with conventional dosesof heparin and aspirin. Baseline angiographic images were recorded asillustrated in FIGS. 13A through 13E. The operator could choose whetheror not to predilate the lesion with conventional transluminalpercutaneous procedures. Next, the CVSi CryoPlasty Catheter was advancedacross the lesion, and the balloon inflated one or more times with theCVSi Cryolnflation Unit. After the final cryotreatment, the balloon wasdeflated and the CVSi Catheter was removed. At the conclusion of theprocedure, a final angiography was recorded as illustrated in FIGS. 13Athrough 13E.

Results

The operators were able to use the CryoPlasty device for primary therapy(i.e. were able to cross severe stenosis and dilate the lesion with theCVSi device without predilation) in all the lesions (100%).Additionally, the CryoPlasty device provided good tracking in vesselswith >90° turns. A total of six lesions were treated (including onepatient who had two lesions in one vessel). All of the lesions treatedhad <30% residual angiographic stenosis in the dilated artery, asillustrated in FIGS. 13A through 13E and the Results Table II. Patientstolerated the procedure well (i.e. no patient sensation of treatment)and four to six week clinical follow-up reports 0% major adverse cardiacevents (MACE).

RESULTS TABLE II CLINICAL SUMMARY OFCORONARY PATIENTS BUC Age/ BaselineResidual # Sex Site Type Factors Stenosis Treatments/Comments Stenosis 164/F LCx prox D Total occlusion, severe 100% (2) CryoPlasty Inflations;20% 20 mm × angulation >100°, some distal dissection grade B-not 2.75 mmcalcification requiring stent placement; No pain 2 55/M LAD prox DStress angina, ST  90% (1) CyroPlasty inflation; 10% 15 mm × changesafter 25 meters, Occlusion angina 3.0 mm 237 chol 3 49/F LAD prox DUnstable angina 7 days  95% (1) CryoPlasty inflation  0% 10 mm × before,admitted, acute subtotal 3.0 mm MI 1996; sig. angulation at bifurcation;allergic to ASA; narrowing back to bifurcation 4 58/F RCA mid IDiabetic, hypertension,  95% (4) CryoPlasty inflations 30% 25 mm ×dyslipidemia, 3.5 PTCA/stent 11/00; PTCA cutting balloon 2/01 RCA prox D 90% (2) CryoPlasty inflations >  0% 10 mm × Grade B-C dissection > 3.53.5 mm × 16 mm stent (post cryo) 5 74/M LCx mid D Colon tumor, surgery 95% (1) CryoPlasty 0% 12 mm × prep; calcification 3.5 mm

Conclusion

Cryogenic treatment of atherosclerotic stenoses may effectively limitrestenosis in both coronary and peripheral arteries, as well as minimizethe amount of vessel dissections and plaque shift post-CryoPlastydilation. Clinical trial data illustrates that CryoPlasty may representa simple solution to one of the most vexing problems experienced to datein interventional therapy.

Although certain preferred embodiments and methods have been disclosedherein, it will be apparent from the foregoing disclosure to thoseskilled in the art that variations and modifications of such embodimentsand methods may be made without departing from the true spirit and scopeof the invention. Therefore, the above description should not be takenas limiting the scope of the invention which is defined by the appendedclaims.

1. A cryotherapy delivery system comprising: a cryotherapy cathetercomprising a catheter body, the catheter configured to deliver acryogenic fluid from a proximal end of the catheter body toward a distalend of the catheter body; and a controller configured to: control a rateof flow of the cryogenic fluid, in response to a measured temperaturereceived via a sensor, to cool an inner surface of a main branch of abifurcated blood vessel having plaque disposed thereon to a temperatureand for a time sufficient to inhibit plaque shift from the main branchinto a side branch of the bifurcated blood vessel, wherein the coolingtime is in a range from about 1 second to less than about 20 seconds,and wherein the cooling temperature of the inner surface of the mainbranch is in a range from about −3° C. to about −15° C.
 2. The system ofclaim 1, wherein the main branch is an artery.
 3. The system of claim 1,wherein the plaque comprises a combination of calcium, fat, and lipids.4. The system of claim 1, wherein the side branch is subject toocclusion by plaque shift from the main branch into the side branch as aresult of treatment of plaque in the main branch.
 5. The system of claim4, wherein the treatment of plaque in the main branch comprises balloonangioplasty.
 6. The system of claim 5, wherein the cooling step isperformed before, during, and/or after balloon angioplasty.
 7. Thesystem of claim 6, wherein the side branch is at least partiallystenosed.
 8. The system of claim 7, wherein the treatment of stenosis inthe side branch comprises balloon angioplasty.
 9. The system of claim 8,wherein the main branch and the side branch are treated simultaneouslyor sequentially.
 10. The system of claim 1, wherein the cooling stepalters mechanical properties of the plaque so that plaque shift from themain branch to the side branch is inhibited.
 11. The system of claim 10,wherein the cooling step solidifies the plaque so that it is lessamorphous.
 12. The system of claim 11, wherein the plaque solidificationis enhanced by the formation of a temporary ice cap on an orifice of theside branch.
 13. A cryotherapy delivery system comprising: a cryotherapycatheter comprising a catheter body, the catheter configured to delivera cryogenic fluid from a proximal end of the catheter body toward adistal end of the catheter body; and a controller configured to controla rate of flow of the cryogenic fluid, in response to a measuredtemperature received via a sensor, to cool a blood vessel lumen definedby a blood vessel wall, with a balloon, to a temperature and for a timesufficient to remodel the blood vessel such that an existing dissectionof the blood vessel wall is reduced.
 14. The system of claim 13, whereincooling the vessel lumen tacks or re-attaches existing vesseldissections into the blood vessel wall.
 15. A cryotherapy deliverysystem comprising: a cryotherapy catheter comprising a catheter body,the catheter configured to deliver a cryogenic fluid from a proximal endof the catheter body toward a distal end of the catheter body; and acontroller configured to control a rate of flow of the cryogenic fluid,in response to a measured temperature received via a sensor, to cool aninner surface of a blood vessel having an existing dissection with theballoon to a temperature and for a time sufficient to tack or re-attacha flap of tissue of the dissection to a blood vessel wall of the bloodvessel.
 16. The system of claim 15, wherein the cooling time is in arange from about 10 seconds to about 60 seconds, and wherein the coolingtemperature of the inner surface of the blood vessel is in a range fromabout −3° C. to about −15° C.
 17. The system of claim 15, wherein theblood vessel is an artery.
 18. The system of claim 15, wherein thedissection comprises flaps, residual plaque, or pieces of tissueresulting from fissuring or tearing of the blood vessel wall or plaquethereon.
 19. The system of claim 15, wherein the dissection at leastpartially blocks the blood vessel.
 20. The system of claim 15, whereinthe dissection limits blood flow.